SNM 2012 Image of the Year

Peptide receptor alpha therapy is well tolerated and has therapeutic effect

June 20, 2012 — The Society of Nuclear Medicine’s (SNM) 2012 Image of the Year illustrates the effectiveness of Bi-213-DOTATOC for the peptide receptor alpha-therapy of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that do not respond to beta therapy. Researchers selected this image from more than 2,000 studies presented over the course of four days during SNM’s 2012 Annual Meeting in Miami Beach, Fla.

Each year, SNM chooses an image that exemplifies the most cutting-edge nuclear medicine or molecular imaging research today and that demonstrates the ability of molecular imaging to detect and diagnose disease and help select the most appropriate therapy. “The images illustrating the effectiveness of Bi-213-DOTATOC for GEP-NETs show the remarkable results that can be achieved in a clinical setting,” said Peter Herscovitch, M.D., chair of SNM’s Scientific Program Committee. “This opens up a new door for those patients whose GEP-NETs do not respond to more standard radiotherapy.”

GEP-NETs are rare, slow-growing tumors that develop in the digestive system and are distributed throughout the body. They fall into two main categories—carcinoid tumors and pancreatic endocrine tumors—and are often resistant to standard chemotherapy. The National Cancer Institute estimates about 1,000 new cases of pancreatic neuroendocrine tumors per year in the United States.

In this study, a Bi-213-DOTATOC was synthesized using a microwave-assisted labeling protocol. Twenty-one patients who had previously shown a resistance to treatment with Y-90 or Lu-177-DOTATOC were treated with escalating doses of the peptide receptor alpha-therapy—from 1-10 GBq up to 21 GBq. Researchers assessed response with Ga-68-DOTATOC PET/CT (positron emission tomography/computed tomography), contrast-enhanced sonography, magnetic resonance imaging, digital subtraction angiography and tumor markers. In addition, markers for hematologic, kidney and endocrine toxicity were monitored during and after treatment.

The labeling protocol for Bi-213-DOTATOC provided reliable doses of the treatment at a clinical level. Patients tolerated the increasing doses well, and there was no acute kidney, endocrine or hematologic toxicity. Shrinkage of primary tumors as well as liver and bone metastases was observed.

Alfred Morgenstern, Ph.D., project leader of the Alpha-Immunotherapy Project at the European Commission, Joint Research Centre, Institute for Transuranium Elements in Karlsruhe, Germany, and lead author of the study, “Synthesis of Bi-213-DOTATOC for peptide receptor alpha-therapy of GEP-NET patients refractory to beta therapy,” noted: “The images illustrate the potential of Ga-68-DOTATOC PET and PET/CT to assess the therapeutic effects we can achieve in multiresistant neuroendocrine tumors with Bi-213-DOTATOC. It’s very exciting to see that peptide receptor alpha therapy with Bi-213-DOTATOC is offering a promising novel therapeutic option for patients refractory to existing therapies.”

PET images (MIP 0-60 min) of three Cynomolgus monkeys. Strong signals are detected at the sites where inserted catheters had roughened surfaces. Almost no other background signal is visible. Only accumulation in the gallbladder becomes visible at the bottom of the image. Credit: Piramal Imaging GmbH, Berlin Germany.

WLE specimen from a patient with a grade 3, ER-/HER2-, no special type (NST) carcinoma. (A) Cerenkov image; (B) Grey-scale photographic image overlaid with Cerenkov signal. An increased signal from the tumor is visible (white arrows); mean radiance is 871 ± 131 photons/s/cm2/sr, mean TBR is 3.22. Both surgeons measured the posterior margin (outlined in blue) as 2 mm (small arrow); a cavity shaving would have been performed if the image had been available intraoperatively. The medial margin (outlined in green) measured >5 mm by both surgeons. Pathology ink prevented assessing the lateral margin; a phosphorescent signal is visible (open arrows). (C) Specimen radiography image. The absence of one surgical clip to mark the anterior margin, and the odd position of the superior margin clip (white arrow) prevented reliable margin assessment. (D) Combined histopathology image from two adjacent pathology slides on which the posterior margin (bottom of image) and part of the primary tumor are visible (open arrows). The distance from the posterior margin measured 3 mm microscopically (double arrow). The medial margin is > 5 mm (not present in image). Credit: A. D. Purushotham, M.D., King’s College London, UK

A 77-year-old male with recurrent lymph node and pulmonary metastases detected by Ga-68 PSMA PET/CT but not by conventional imaging. Graphic courtesy of the Department of Nuclear Medicine, Royal North Shore Hospital, Sydney